AB0350 ASSESSMENT OF REAL-LIFE PATIENT HANDLING EXPERIENCE OF AVT02 ADMINISTERED SUBCUTANEOUSLY VIA AUTOINJECTOR IN PATIENTS WITH MODERATE-TO-SEVERE ACTIVE RHEUMATOID ARTHRITIS: AN OPEN-LABEL, SINGLE-ARM CLINICAL TRIAL, THEN AN EXTENSION PHASE OF AVT02 ADMINISTERED WITH A PRE-FILLED SYRINGE (ALVOPAD-PEN)
Authors: N. Damjanov, H. Stroissnig, M. Steiger, J. Sobierska, E. Guenzi, H. Otto, A. Sattar, H. N. Haliduola, E. Edwald, F. Berti
Journal: Annals of the Rheumatic Diseases (2022)

Background AVT02 is an investigational biosimilar to adalimumab. It is approved in Europe, Canada, and the UK. It is not approved by the US Food and Drug Administration (FDA). Objectives To assess the real-life patient handling of an autoinjector (AI) in adult patients with moderate-to-severe active rheumatoid arthritis (RA) who self-inject AVT02 subcutaneously (s.c.). Methods This open-label study enrolled 107 adalimumab-naïve subjects with moderate-to-severe active RA to self-inject AVT02 with the proposed AI 40 mg s.c. in Week 1, and every other week thereafter through Week 8. In an optional extension phase through Week 56, subjects were switched from AVT02 AI to pre-filled syringe and followed for safety and efficacy. The primary endpoint was the percentage of successful self-injections as reported by both the trial site and by subjects using standardized questionnaires at Week 8. Additional endpoints included ease of use and robustness of the AI at Week 8, and efficacy in RA, assessment of serum trough levels of AVT02, and detection of antidrug antibodies (ADA) throughout the study. Results The AI success rate was 100% as reported by both the trial site and by subjects. No handling events were noted through Week 8. Approximately 80% (78.1–84.9%) of subjects found the AI ‘very easy’ to use and, in general, less difficulty was reported as the study progressed. The first 110 AIs used were inspected for robustness and none showed any sign of damage or malfunction. All subjects who completed Week 8 (n = 106) took part in and completed the optional extension phase through Week 56. At Week 8, 49.1%, 5.7% and 0.9% subjects achieved ACR20, -50 and -70 responses, respectively. Improvement was also reported for the SDAI, DAS28 CRP and HAQ, with scores consistently decreasing through Week 8. In the extension phase, 70.8%, 47.2% and 13.2% subjects achieved ACR20, -50 and -70 responses at Week 56. Improvement was also reported for the SDAI, DAS28 CRP and HAQ, with scores consistently decreasing through Week 56. From Baseline through Week 8 the mean serum concentrations of investigational AVT02 increased consistently at each visit, reaching a peak at Week 24. There was no significant difference in serum concentrations of AVT02 based on injection subsite (abdomen or thigh). ADAs were detected in 65.1% of subjects through Week 8, reducing to 49.1% by Week 56. Of ADA-positive subjects, most were also positive for neutralizing antibodies through Week 8 (62.3%) increasing through Week 56 (90.4%). Subjects who were ADA-positive had lower serum concentrations of study drug compared with the overall population at Week 8 and Week 56 as expected. There were no clinically relevant safety or tolerability issues. Overall, treatment-emergent adverse events reported in at least 5% of subjects at the PT level were anaemia and influenza (6 subjects [5.6%)] reported 6 events each), and no local ISRs were reported. Conclusion The fully successful self-injection with the AI in this study supported the use of the device while administering AVT02. Furthermore, subjects typically found the AI easy to use, with ease of use increasing as time progressed. The ACR20, -50, and -70, SDAI, DAS28 CRP and HAQ results supported the use of AVT02 to treat adult patients with moderate-to-severe RA, with the treatment effect persisting beyond Week 8 and through Week 56. The safety and immunogenicity profiles were as expected for adalimumab. ClinicalTrials.gov Identifier: NCT04224194 Disclosure of Interests Nemanja Damjanov: None declared, Heimo Stroissnig Employee of: Alvotech, Matjaz Steiger Employee of: Alvotech, Joanna Sobierska Employee of: Alvotech, Eric Guenzi Employee of: Alvotech, Hendrik Otto Employee of: Alvotech, Abid Sattar Employee of: Alvotech, Halimu N. Haliduola Employee of: Alvotech, Elin Edwald Employee of: Alvotech, Fausto Berti Employee of: Alvotech